RATIONALE: Biological therapies, such as CpG 7909, use different ways to stimulate the
immune system and stop cancer cells from growing.
PURPOSE: This randomized phase I/II trial is studying the side effects of CpG 7909 and to
see how well it works in treating patients with cutaneous T-cell lymphoma.
- Determine the safety of CpG 7909, in terms of adverse events, vital signs, and
laboratory and clinical findings, in patients with stage IB-IVA cutaneous T-cell
- Determine tumor response, as measured by the Composite Assessment of Index Lesion
Disease Severity (CA), in patients treated with this drug.
- Determine the tolerability of this drug in these patients.
- Determine the immunopharmacodynamics of this drug in these patients.
- Determine disease response, based on the Physician Global Assessment of Clinical
Condition (PGA), in patients treated with this drug.
- Determine duration of response, based on the CA and PGA, in patients treated with this
- Determine time to response in patients treated with this drug.
- Determine time to progression in patients treated with this drug.
OUTLINE: This is a phase I, open-label, multicenter, dose-escalation study followed by a
randomized phase II study.
- Phase I: Patients receive CpG 7909 subcutaneously (SC) once weekly on weeks 1-24 in the
absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of CpG 7909 until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
- Phase II: Patients are randomized to receive 1 of 2 doses of CpG 7909, administered as
in phase I.
Patients are followed every 4 weeks.
PROJECTED ACCRUAL: A total of 3-56 patients (3-36 for phase I and 20 [10 per treatment arm]
for phase II) will be accrued for this study.
- Histologically confirmed cutaneous T-cell lymphoma (CTCL) (limited to mycosis
- Stage IB-IVA disease
- No other cutaneous lymphomas including, but not limited to, CD30-positive
large-cell T-cell lymphoma, lymphomatoid papulosis, and pagetoid reticulosis
- No visceral disease (stage IVB CTCL)
- Must have received 1-3 prior systemic regimen(s), including psoralen ultraviolet
light therapy (PUVA)
- No CNS disease
- 18 and over
- Karnofsky 60-100%
- More than 4 months
- Neutrophil count ≥ 1,000/mm^3
- Platelet count > 100,000/mm^3
- WBC > 4,000/mm^3
- Hemoglobin ≥ 10 g/dL
- Bilirubin ≤ 1.5 mg/dL
- SGOT or SGPT < 3 times upper limit of normal
- PTT ≤ 40 seconds
- No active hepatitis B or C
- Creatinine ≤ 2.0 mg/dL
- No unstable angina
- No New York Heart Association class III-IV congestive heart failure
- No myocardial infarction within the past 6 months
- No uncontrolled atrial or ventricular cardiac arrhythmias
- No other significant cardiovascular disease
- HIV negative
- No autoimmune or antibody-mediated disease, including any of the following:
- Systemic lupus erythematosus
- Rheumatoid arthritis
- Multiple sclerosis
- Sjögren's syndrome
- Autoimmune thrombocytopenia
- Controlled thyroid disease allowed
- Autoantibodies without clinical autoimmune disease allowed
- No history of allergic reactions attributed to compounds of similar composition to
- No fever ≥ 38.2°C within the past 24 hours
- No serious, symptomatic, significant local or systemic infection, including urinary
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 weeks after study
- No suspected or confirmed poor compliance, mental instability, or prior or current
alcohol or drug abuse that would preclude study participation or giving informed
- No other medical history, including laboratory results, that would preclude study
- No other malignancy within the past 5 years except basal cell or completely excised
non-invasive squamous cell skin cancer or squamous cell carcinoma in situ of the
PRIOR CONCURRENT THERAPY:
- No concurrent denileukin diftitox
- No other concurrent immunotherapy, including but not limited to, interleukin-2,
interferon (IFN) alfa, or IFN gamma
- At least 4 weeks since prior systemic chemotherapy for CTCL
- No concurrent chemotherapy
- No concurrent topical or systemic corticosteroids
- At least 4 weeks since prior electron beam therapy for CTCL
- No concurrent radiotherapy
- More than 6 months since prior coronary angioplasty
- At least 2 weeks since prior topical therapy for CTCL
- At least 3 weeks since prior phototherapy for CTCL
- At least 4 weeks since prior photopheresis for CTCL
- At least 4 weeks since other prior systemic therapy for CTCL
- At least 4 weeks since prior daily systemic cholecalciferol (vitamin D) > 15,000 IU
- At least 4 weeks since prior oral retinoids, including bexarotene for CTCL
- At least 4 weeks since prior investigational therapy for CTCL
- No prior treatment for hepatitis B or C
- More than 2 weeks since prior systemic antibiotics for CTCL
- Patients receiving systemic antibiotics for CTCL must be on a stable regimen for
at least 2 weeks before study entry
- More than 30 days since prior participation in an investigational drug trial
- No concurrent chloroquine phosphatase
- No concurrent anticoagulant therapy except aspirin (≤ 325 mg/day)
- No concurrent phototherapy
- No concurrent photopheresis therapy
- No concurrent bexarotene
- No concurrent immunosuppressants
- No other concurrent investigational drugs